Delivery devices for administering a beneficial agent to a biological fluid environment of use are known in the prior art. Representative examples of various types of delivery devices are disclosed in U.S. Pat. Nos. 3,845,770; 3,916,899; 3,995,632; 4,111,202; 4,111,203; 4,203,439; 4,327,725; and 4,612,008; al of which are incorporated herein by reference. The delivery devices described in the above patents operate successfully for their intended use and they can deliver many beneficial agents for their intended effects. However, it has been observed that their use can be limited because they lack the necessary elements to deliver beneficial agents that are sensitive to fluids and to fluids containing biological gases. Their use may be limited because beneficial agents that are sensitive to such aqueous biological fluids or to other fluids external to the delivery device may be adversely affected by fluids that enter the device and contact the beneficial agents during operation of the device. Examples of such fluid-sensitive agents include proteins, peptides, and hormones. Moreover, the prior art devices lack the necessary means for their use as implant devices for dispensing such sensitive agents to a biological fluid-rich environment of use.
To overcome the limitations associated with the prior art delivery devices, a delivery device was developed and is described and claimed in copending, commonly-assigned patent application U.S. Ser. No. 07/283,359, filed Dec. 13, 1988, now issued as U.S. Pat. No. 5,034,229 to Magruder et al. for Delivery System Comprising Means for Governing Fluid Ingress into the System. This delivery device comprises a compartment, one portion of which is substantially impermeable to fluid and contains a fluid-sensitive drug protected from a fluid environment, and a second portion of which is permeable to fluid and contains an expandable driving means for administering the drug to the fluid environment of use. The system has been found to be particularly useful as an implant in livestock for delivering a fluid-sensitive drug over a broad range of dosage delivery rates according to a predetermined time-release pattern.
A disadvantage recently discovered with the devices of U.S. Pat. No. 5,034,229 is that, in order for the drug reservoir portion and the fluid-permeable portion of the device to be adhesive bonded at their lap joints to produce a hydrostatically intact seal under internal back pressure up to 15 psi, the materials of the two portions must dissolve in similar solvents. A simple pressure-sensitive adhesive will not provide an adequate seal between the straight edges of the two portions. As a consequence of this limitation, the materials which must be used for the drug reservoir, in order to form an adhesive bond seal with the dimensionally unstable and thin fluid-permeable membrane, must have, in fact, a finite osmotic permeability to water. At the same time, certain stable and resorbable somatotropin formulations to be delivered are osmotically active, having the same osmotic activity as a saturated solution of sodium chloride; additionally, these agents, as well as other proteins and peptides, are labile and will aggregate in the presence of water. The combination of these characteristics results in absorption of some water through the reservoir wall and dilution and some inactivation of beneficial agent inside the reservoir. In vitro and in vivo testing results from prior art devices according to U.S. Pat. No. 5,034,229 have demonstrated up to 20-25% dilution of a somatotropin fluid-sensitive beneficial agent formulation at 4-5 weeks of delivery.
Accordingly, it is desirable to provide a delivery device that provides improved stability for the benficial agent formulation in vivo; that is, it does not cause the dilution and inactivation of an active agent to be delivered by the device.